Objective:To investigate the effects of antidepressants on longevity, age at dementia onset, and survival after onset among adults with Down syndrome, controlling for late-onset seizures, trisomy 21 mosaicism, and cholinesterase inhibitor use.

Method: The charts of 357 adults with Down syndrome (mean age at first visit=46.3 years, SD=9.0) evaluated in a metropolitan diagnostic and research clinic between 1990 and 2008 were reviewed. Seventeen patients had trisomy 21 mosaicism; 155 patients were diagnosed with depressive disorders using DSM-III-R and IV criteria, 78 of whom received antidepressants for over 90 days. Of 160 patients who developed dementia, the estimated mean age at onset was 52.8 years. Fifty-six patients (demented and nondemented) had late-onset seizures. Longevity and age at estimated onset among those receiving and not receiving antidepressants were compared. Cox proportional hazards models examined risks for dementia onset and death.

Results: The mean age at dementia onset among those receiving antidepressants before onset was 53.75 years versus 52.44 years among others. Proportional hazards models showed a significant delay of onset among those taking antidepressants (hazard ratio=0.69; 95% CI, 0.48–0.98; P=.038). Mean age at death or at end of study for those receiving antidepressants was 54.71 years; among others, it was 52.60 years (hazard ratio=0.63; 95% CI, 0.42–0.94; P=.024). Among the 35 adults with late-onset seizures and dementia who died, mean survival after seizure onset was 4.23 years.

Conclusions: The findings in this retrospective study revealed that antidepressant use was associated with delayed dementia onset and increased longevity in adults with Down syndrome; mean survival after late-onset seizures was longer than previously reported. Further studies, however, are needed to confirm these associations, optimally in a clinical trial to confirm causality.